The gut is a tube and inside the tube there are groups of neurons that line the gut and are important for ingestion, digestion, and excretion and host defense.
It is called the enteric nervous system (ENS).
Autonomic nerves
Vagal and pelvic pathways
Sympathetic
Autonomic
Sensory, afferent
Autonomic
Consists of neurons and glial
Has as many neurons as the spinal cord
Contains multiple neurotransmitters and messenger systems like the brain
Independently controls gut function (this is what really distinguishes it)
When you put stimulus in the gut, contraction occurs orally and relaxation occurs anally and creates propulsion down the gut.
If you cut nerves to the gut, it will still push stimulus through it. If you cut nerves to the heart (or other organs), it will stop working. When you paralyze the nerves in the ENS, it can't move the stimulus along but there are still contractions. This proves the ENS is what controls the movement along the gut, and can work by itself
Enteroendocrine cells
They release chemicals to activate sensory nerves that lie in the two plexuses, which then activate interneurons. It activates motor neurons in the oral direction, which are excitatory, and give rise to contractions. The activate inhibitory neurons in the anal direction which give rise to relaxation.
This contraction and relaxation set up the pressure gradient.
Reflexes are modified by glial cells, they play an important role in the ENS.
Enteroendocrine, neural, and glial signaling
Inhibitory: Nitric Oxide
Excitatory: Acetylcholine
Co-transmitters: substance P and other peptides
Oral end, anal end
Community of 100+ trillion microrganisms (viruses, bacteria, protozooans, archea, and fungi
Mutualistic (they benefit the host and the microbiome)
Its metabolic output is so vast and so important it is considerd its own organ
The gut has the largest proportion of microbes than any other site in the body
False. The gut microbiome comes from your mother by way of birth (vaginally, c-section, etc)
Babies are born 'sterile.' They gets 'bugs' and takes about 5-10 years to become stable. It is influenced during puberty, becomes fully developed in late teens or early 20s. Can be affected by early life factors (antibiotics, diet, genetics)
Metabolic role, role in inhibition of pathogenic bacteria, and developmental/defensive role
Digests food that can't be digested
Promote digestion and energy utilization: fermentation of non-digestible food
Facilitate absorption of dietary minerals
-Synthesis of metabolites (short chain fatty acids, vitamin K, B12, biotin etc)
Microbiome possess the enzymatic tools to degrade and synthesize a large variety of compounds
Protects against microbes, toxins, etc.
Development of the intestinal mucosa and immune system
Microbiome stimulate production of regulatory T cells
Short chain fatty acids (acetate, butyrate, etc)
Microbe-associated molecular patterns (TLR ligands, NLR ligands)
Ligand-activated transcription factor receptor ligands (tryptophan metabolites)
Quorum sensing molecules (acyl homoserine lactones) (microbiota talk to eachother through quorom sensing molecules)
Humoral pathway: Cytokines from activate monocytes and macrophages enter the brain through CVOs (leaky areas of the blood brain barrier)
Neural pathway: Cytokines from activated monocytes and macrophages stimulate nerve fibres in the vagus nerve, which then relays information to the brain (direct stimulation between the gut and the brain)
Cellular pathway: Cytokines stimulate microglia which produce MCP-1, which recruits monocytes into the brain.
Sensory
Nerves don't penetrate beyond the epithelium, so nerves in the gut going to the brain need a transducer to know whats doing on in the lumen. The transducers are the enteroendocrine cells (specialized epithelial cells)
Located throughout the length of the GI tract. Different types line different areas of the gut and signal using different molecules (peptides and biological amine (5-HT))
Microbial signals.
Bacteria talk to enteroendocrine cells and E cells talk to the immune system
Serotonin (5-HT)
The majority of the body's serotonin is in the bowel, and most 5-HT in the bowl is synthesized by enterchromaffin (EC) cells.
5-HT released from EC cells can initiate reflex responses, such as intestinal secretion and peristalsis, and when released in large amounts it can cause nausea and vomiting
5-HT actions are terminated by reuptake involving the same serotonin-selective transporter (SERT) that is found in the CNS
Bacteria/ gut microbes.
If you don't have bacteria you will have less 5-HT and slower function.
Neural (enteric and autonomic)
Glial
Enteroendocrine
Microbial
Immunological pathways
Mechanical
Chemical
Toxins
Radiation
Mechanosensitivity.
The gut has a sense of touch using the same mechanosensitive channels that are used for sense of touch in the skin.
Neuropods cells are in the intestinal epithelium and contain both large dense-core neuropeptide vesicles and small neurotransmitter vesicles. They have the capacity to receive afferent signalling from lumin from enteroendocrine cells to nerves, and also efferent signaling.
Glutamate
Afferent nerves involve fast neurotransmission. Enteroendocrine cells can release glutamate and signal to nerves in a fast neurotransmitter.
GLP-1 release (GLP-1 regulates glucose uptake and brain blood flow, regulating glucose utilization in the liver and brain)
Brain glucose utilization
Cognitive function
This is an example of gut-brain communication involving autonomic nerves regulating gut peptide release to influence learning and memory
a-synuclein
Enteroendocrine cells express a-synuclein, misfolding of this can lead to neurodegenerative diseases. A-synuclein is able to transmit to the nerves that underly it, then goes through the vagus to the brain stem (why PD patients have brain stem lesions before motor lesions in the substantia nigra and basal ganglia
Germ free rats have altered small intestinal transit. Germ free anything has slower motility.
They are mostly likely to be impacted by the gut microbiome
They are a specific type of enteric neuron.
Resting membrane potential is around -65mV
Rapid accomodation
Prolonged afterhyperpolarization
Spontaneous activity is rare
Slow excitatory synaptic potentials are common, but fast synaptic potentials are rare
Microbial products and probiotic bacteria
Electrophysiological recordings of enteric primary afferent neurons showed short chain fatty acids specifically stimulate those nerves and microbial products are involved in activating those nerves.
Enteric microbiota
Action potential threshold activation is higher in germ free mice and they fire less action potentials (they are less excitable)
It alters fluid balance and intestinal transit (changes water balance in the gut)
The gut will completely recover after stopping antibiotics.
If there is enough antibiotics to kill everything in the gut, you will lose enteric neurons.
1. They mediate glial homeostasis in the mucosa of the GI tract.
Neurons and glial are regulated by the prescence of microbiota
In germ free mice there are less glial cells.
2. They mediate bacterial signaling to innate immune cells (type 3 innate lymphoid cells) to provide IL-22 via neurotrophic factor signaling.
Aka. Important for immune function because they regulate the immune system
5-HT4 receptors
Serotonin is important in enteric neuronal homeostasis
1. The microbiota alters gut function in germ free mice.
Mice got the same IBS symptom as the human donor.
2. The microbiota alters behaviour in germ free mice.
Mice got anxiogenic effects from human donors with anxiety (due to change in BDNF levels)
You will stimulate the mouse's ability to run on a wheel. If you deplete the microbiota, you deplete their motivation to run.
This is due to striatal dopamine mediated by gut sensory nerves that are regulated by endocannabinoids.